Many attempts at mass production of useful proteins utilizing gene recombination techniques have been done by using prokaryotes such as Escherichia coli, Bacillus subtilis and the like as hosts, and eukaryotes such as yeast, animal cells and the like. Firstly, techniques for producing and accumulating the desired products in microbial cells have been established, and such techniques have been utilized for the production of useful proteins such as interferons, cytokines, hormones and the like by using Escherichia coli or Bacillus subtilis. However, when products are accumulated in microbial cells, there are problems that the amount of an accumulated product is limited and, sometimes, only an inactive product is produced. Then, various attempts for production and secretion of products outside of microbial or animal cells have also been done by using Bacillus subtilis, yeast, animal cells and the like.
On the other hand, it has been known for long time that molds secrete enzymes in an extremely large amount, and they have been noted as a host for gene recombination. In this respect, production-by-secretion systems using molds belonging to the genera Aspergillus, Trichoderma, Mucor and the like have been reported. However, such systems are not always well established industrially.
In order to establish an efficient production-by-secretion process of proteins, powerful promoters and secretion signals which are operable in a host organism to be used are essential. The efficiency of the promoter and secretion signal varies according to particular kinds of host organisms. Further, the efficiency also varies according to nucleotide sequences of genes coding for the desired proteins or the protein structure. Therefore, powerful new promoters and secretion signals have been under investigation.